NUTRIM School for Nutrition, Toxicology, and Metabolism, Department of Human Biology, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.
J Clin Endocrinol Metab. 2012 Jan;97(1):208-16. doi: 10.1210/jc.2011-1884. Epub 2011 Oct 26.
Animal studies revealed that medium-chain fatty acids (MCFA), due to their metabolic characteristics, are not stored in skeletal muscle and may therefore not give rise to potentially hazardous lipid species impeding insulin signaling.
We here hypothesized that infusion of medium-chain triacylglycerols (MCT) in healthy lean subjects does not lead to ectopic fat accumulation and hence does not result in lipid-induced insulin resistance.
Nine healthy lean male subjects underwent a 6-h hyperinsulinemic-euglycemic clamp with simultaneous infusion of 1) a 100% long-chain triacylglycerols (LCT) emulsion, 2) a 50/50% MCT/LCT emulsion, or 3) glycerol in a randomized crossover design. Muscle biopsies were taken before and after each clamp.
MCT/LCT infusion raised plasma free fatty acid levels to a similar level compared with LCT infusion alone. Despite elevated free fatty acid levels, intramyocellular triacylglycerol (IMTG) levels were not affected by the MCT/LCT emulsion, whereas LCT infusion resulted in an approximately 1.6-fold increase in IMTG. These differences in muscle fat accumulation did not result in significant differences in lipid-induced insulin resistance between LCT (-28%, P = 0.003) and MCT/LCT (-20%, P < 0.001). Total skeletal muscle ceramide content as well as lactosyl- and glucosylceramide levels were not affected by any of the interventions. In addition, the distribution pattern of all ceramide species remained unaltered.
Although we confirm that MCFA do not lead to ceramide and IMTG accumulation in skeletal muscle tissue in humans, they do induce insulin resistance. These results indicate that, in humans, MCFA may not be beneficial in preventing peripheral insulin resistance.
动物研究表明，中链脂肪酸（MCFA）由于其代谢特性，不会储存在骨骼肌中，因此不会产生潜在有害的脂质种类，从而阻碍胰岛素信号传导。
我们假设在健康的瘦受试者中输注中链三酰甘油（MCT）不会导致异位脂肪堆积，因此不会导致脂质诱导的胰岛素抵抗。
9 名健康的瘦男性受试者接受了 6 小时的高胰岛素-正常血糖钳夹实验，同时输注 1）100%长链三酰甘油（LCT）乳剂，2）50/50% MCT/LCT 乳剂，或 3）甘油，采用随机交叉设计。在每次钳夹前后取肌肉活检。
MCT/LCT 输注使血浆游离脂肪酸水平升高至与单独输注 LCT 相似的水平。尽管游离脂肪酸水平升高，但 MCT/LCT 乳剂并未影响肌内三酰甘油（IMTG）水平，而 LCT 输注导致 IMTG 增加约 1.6 倍。这些肌肉脂肪堆积的差异并未导致 LCT（-28%，P=0.003）和 MCT/LCT（-20%，P<0.001）之间脂质诱导的胰岛素抵抗有显著差异。LCT 和 MCT/LCT 输注均不影响总骨骼肌神经酰胺含量以及乳糖基和葡萄糖基神经酰胺水平。此外，所有神经酰胺种类的分布模式均未改变。
尽管我们证实 MCFA不会导致人体骨骼肌组织中神经酰胺和 IMTG 堆积，但它们确实会引起胰岛素抵抗。这些结果表明，在人类中，MCFA可能无益于预防外周胰岛素抵抗。
